The human cytokine polypeptide of the present invention has a high degree of similarity to the Drosophila twisted gastrulation gene and also has homology to human connective tissue growth factor.
The twisted gastrulation gene (TSG) is one of seven known zygotic genes that specify the fate of dorsal cells in Drosophila embryos. Mutations in these genes cause at least some of the cells on the dorsal half of the embryo to adopt more ventral cell fates leading to the proposal that most of these genes participate in establishing, maintaining or modulating a gradient of a single signaling molecule decapentaplegic. The effects of TSG mutations on the development of cuticle elements, expression of a region specific enhancer trap and patterns of mitotic domains have been examined Mutations of TSG only affect the fate of a narrow strip of dorsal midline cells and do not affect dorsal ectoderm cells. However, the pattern of TSG expression is not coincident with the territories affected by TSG mutations. Structural analysis of the TSG gene reveals features of a secreted protein suggesting an extra cellular site of action. The TSG protein bears a weak resemblance to human connective tissue growth factor (CTGF), a TGF--induced protein. The dorsal midline cell fate is specified by the combination of both a TSG and a decapentaplegic signal to which the dorsal midline cells are uniquely competent to respond. Mason, E. D. et al., Genes Dev., 8:1489-1501 (1994).
Accordingly, there is a need in the art for identification and characterization of proteins that influence biological activity, both normally and in disease states. In particular, there is a need to isolate and characterize human cytokine polypeptides akin to the TSG gene found in Drosophila which may be employed, therefore, for preventing, ameliorating or correcting dysfunctions or disease or augmenting positive natural actions of such genes.